In situ forming polymer foams, such as the Arsenal Foam Technology commercialized by Arsenal Medical (Watertown, Mass.), have a number of important biomedical applications including the prevention or treatment of hemorrhage, particularly from noncompressible or difficult-to-visualize wounds, vascular embolization, arteriovenous malformation, AV fistulas, abdominal aortic aneurysm, space filling and bulking (e.g. following surgical resection, or for cosmetic purposes), prevention of tissue adhesion, hernia repair, prevention or treatment of reflux, and temporary or permanent occlusion of body lumens for a variety of applications including sterilization, prevention of calculus migration during lithotripsy, and other applications. The diversity of applications for in situ forming foams reflects significant advantages possessed by such foams relative to existing technology, including, without limitation their incorporation of well characterized, biocompatible materials; the ability to deliver in situ forming foams to closed cavities, for example intravascularly; the ability to deliver in situ forming foams to difficult-to-access body sites; the ability of in situ forming foams to expand into empty space, potential space, or into space filled with blood, support surrounding tissues, and the ability of the foam to fill a body cavity.
Foams are typically generated in situ by delivering and mixing multiple liquid-phase components (such as a polyol component and an isocyanate component, which form a polyurethane foam). Pores within the foam may be formed by a blowing reaction and/or by the entrainment of gas before or during foam formation, and the foam may harden through the formation of cross-links between prepolymers and/or cross-linking agents. When deployed into a body cavity, the liquid components react, driving the expansion and hardening of the foam. The foam applies pressure to the boundaries of the cavity in a dose dependent and time-dependent manner, for example as shown in the pressure curves of FIG. 1. The shapes of these curves are determined by, among other things, the composition and quantity of liquid phase components applied to the body cavity, which govern the rates of the blowing and cross-linking reactions and foam properties (e.g., density or volume expansion, stiffness, pore size, hydrophilicity, absorption capacity).
In situ forming foams are particularly well suited to treating noncompressible hemorrhages in challenging settings, including the battlefield and rural or wilderness settings far from hospital trauma centers. However, in spite of their advantages, in situ forming foams have not been widely used because of the technical challenges associated with developing suitable in situ foaming formulations for different applications and delivering of these formulations to body cavities in quantities sufficient to arrest hemorrhages without causing undesirable side effects of excessive pressure such as compartment syndrome. Additionally, to maximize their efficacy in challenging or remote settings, in situ forming foams should extend patient survival times for a period sufficient to permit evacuation of patients to stations or centers where hemorrhages can be surgically treated.